Triethylamine → 3,5-dichlorobenzyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

HRID 856327Notes

Reaction equation

HRID 856327 reaction equation
Cl.Cl.[CH3:3][C@@:4]1([CH2:15][N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[O:8][C:7]2=[N:9][C:10]([N+:12]([O-:14])=[O:13])=[CH:11][N:6]2[CH2:5]1.C(N(CC)CC)C.[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([Cl:38])[CH:37]=1)[CH2:33][OH:34].[C:39](N1C=CN=C1)(N1C=CN=C1)=[O:40]>O.CN(C=O)C>[CH3:3][C@@:4]1([CH2:15][N:16]2[CH2:17][CH2:18][N:19]([C:39]([O:34][CH2:33][C:32]3[CH:31]=[C:30]([Cl:29])[CH:37]=[C:36]([Cl:38])[CH:35]=3)=[O:40])[CH2:20][CH2:21]2)[O:8][C:7]2=[N:9][C:10]([N+:12]([O-:14])=[O:13])=[CH:11][N:6]2[CH2:5]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 432363,5-Dichlorobenzylic alcoholHCID 682631,1'-CarbonyldiimidazoleHCID 69481767(S)-2-methyl-6-nitro-2-(piperazin-1-ylmethyl)-2,3-dihydroimidazo[2,1-b]oxazole dihydrochloride

Product 1

HCID 696353023,5-dichlorobenzyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylateYield 53.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of (S)-2-methyl-6-nitro-2-(piperazin-1-ylmethyl)-2,3-dihydroimidazo[2,1-b]oxazole dihydrochloride prepared in Example 408 (300 mg, 0.88 mmol) and DMF (3 ml), triethylamine (270 mg, 2.67 mmol) was added for neutralization. To the solution, a mixture of 3,5-dichlorobenzyl alcohol (180 mg, 1.02 mmol), DMF (3 ml) and 1,1′-carbonyldiimidazole (180 mg, 1.11 mmol) stirred at room temperature for 2 hours was added followed by stirring at room temperature overnight. To the reaction mixture, water was added, and the mixture was extracted with ethyl acetate twice. The organic phases were combined, washed with water twice and a saturated saline solution, dried over sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate) to afford 3,5-dichlorobenzyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate (220 mg, yield 53%) as a white powder.

Workup

  1. additionwas added for neutralization
  2. additionwas added
  3. stirringby stirring at room temperature overnight
  4. extractionthe mixture was extracted with ethyl acetate twice
  5. washwashed with water twice
  6. dry with materiala saturated saline solution, dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-a64a91d167fc4797b73d6299a6b63b7c
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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